Liver injury caused by drugs and chemicals is a problem that continues to grow in prevalence and importance. Drug induced liver injury (DILI) is a common cause of acute liver failure in the United States, accounting for about 13% of such cases (1-3). DILI is also the most frequent adverse drug event that leads to the abandonment of otherwise promising new drug candidates or to the withdrawal from the market of new drugs, often after only months of use. Such occurrences have obvious and major human costs, in terms of pain, suffering, and death experienced by those who develop DILI, but also major economic costs to the companies that have developed these drugs, to their shareholders, and to society at-large because the resources that went into development of such doomed drugs might have been better spent on other measures to improve our health and well-being (4-7).
The prevalence of DILI is compounded by the growing use of herbal remedies and dietary supplements (HDS). These are often assumed to be safe because they are “natural.” However, it is clear that many of these may cause serious liver injury. In recent years, about 10% of DILI instances in the U.S. have involved HDS (10), and even higher frequencies have been reported in the Far East (11).
In addition to DILI, the liver of a mammal can be damaged in a variety of other ways, including inflammation due to a viral infection (e.g., Hepatitis A, B, C, or E), obstruction of bile flow, accumulation of cholesterol or triglycerides, and compromised blood flow to the liver.
Regardless of its etiology, liver damage can be hard to diagnose. Commonly used biomarkers for liver damage, such as serum aminotransferases, alkaline phosphatase, and other enzymes, have limited sensitivity and specificity (7,9). Furthermore, providing an accurate prognosis for liver damage is even more difficult. For patients suffering from acute liver failure, there are no reliable tests to predict whether a liver transplant will be necessary in the near term (e.g., a six month time frame). Because of the limited supply of livers for transplant surgery, it is critically important to distinguish between patients that will require a transplant in the near term and patients that will not.
Accordingly, there remains an urgent need for methods and kits for accurately detecting liver damage and predicting the survivability of subjects suffering from life-threatening liver damage within a given time-frame.